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1.
Plast Reconstr Surg ; 153(2): 346-350, 2024 02 01.
Article in English | MEDLINE | ID: mdl-36988638

ABSTRACT

SUMMARY: Adequate nasal tip projection remains a challenge in aesthetic rhinoplasty for East Asians. Various surgical techniques have been developed to reshape the nasal tip using auricular cartilage. In this article, we introduce the new ram graft to increase nasal tip projection by using one complete piece of conchal cartilage. Between 2019 and 2021, 19 patients who underwent nasal tip reconstruction using ram grafts were reviewed in a single hospital. The complication rate, satisfaction rate, and changes in nasolabial angle and nasal proportion were recorded. Nineteen patients with a mean age (± SD) of 28.9 ± 6.1 years underwent nasal tip reconstruction. The mean follow-up time was 15.4 ± 6.6 months. Nasolabial angle increased from 87.4 ± 10.0 degrees to 91.2 ± 10.2 degrees ( P > 0.05). Sixteen of 19 patients (84.2%) were satisfied with their results. The nasal length-to-nasal tip projection-to-dorsal height-to-radix height ratio is 2:0.8:0.62:0.19 preoperatively and 2:0.92:0.77:0.35 postoperatively. Complications including alloplast-related infection (two of 19) and septal extension graft-related decrease of nasal tip projection (one of 19) were recorded. By using one complete piece of conchal cartilage, the ram graft is a simple and effective approach to increase nasal tip projection for East Asians. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Ear Auricle , Rhinoplasty , Humans , Young Adult , Adult , Nose/surgery , Rhinoplasty/methods , Ear Cartilage/surgery , Esthetics , Ear Auricle/surgery , Nasal Septum/surgery , Retrospective Studies , Treatment Outcome
2.
Article in English | MEDLINE | ID: mdl-36688881

ABSTRACT

Kaposiform hemangioendothelioma is a locally invasive tumor and we were unable to find any previous reports of multifocal progression. Sirolimus, a mammalian target of rapamycin inhibitor, has been widely used to treat kaposiform hemangioendothelioma. Herein, we report a case of multifocal progressive kaposiform hemangioendothelioma, wherein sirolimus treatment caused severe thrombocytopenia. A 12-year-old East Asian girl presented with indurated dark-purple masses on her back. The patient had received three surgical interventions following the first appearance of the masses in 2012 and subsequent reappearances in 2014 and 2016. Kaposiform hemangioendothelioma was diagnosed based on radiological and pathological findings. Two more masses appeared in the following year. The patient was treated with oral sirolimus (2.5 mg/ m2/day) and developed grade 3 thrombocytopenia 8 days later. The patient was uneventfully relieved 5 days later after the withdrawal of sirolimus and the administration of appropriate medications. This rare case indicated that kaposiform hemangioendothelioma could be progressive with local metastatic characteristics in children. Besides, the severe sirolimus-induced complication highlights the importance of serum drug level monitoring during treatment. Physicians should be extremely cautious while treating kaposiform hemangioendothelioma patients with sirolimus.


Subject(s)
Anemia , Hemangioendothelioma , Kasabach-Merritt Syndrome , Sarcoma, Kaposi , Child , Female , Humans , Anemia/chemically induced , Hemangioendothelioma/diagnosis , Hemangioendothelioma/drug therapy , Kasabach-Merritt Syndrome/diagnosis , Kasabach-Merritt Syndrome/drug therapy , Sarcoma, Kaposi/chemically induced , Sarcoma, Kaposi/diagnosis , Sarcoma, Kaposi/drug therapy , Sirolimus/adverse effects
3.
Angew Chem Int Ed Engl ; 60(40): 21713-21717, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34350671

ABSTRACT

Subnanometric metal clusters have attracted extensive attention because of their unique properties as heterogeneous catalysts. However, it is challenging to obtain uniformly distributed metal clusters under synthesis and reaction conditions. Herein, we report a template-guidance protocol to synthesize subnanometric metal clusters uniformly encapsulated in beta-zeolite, with the metal ions anchored to the internal channels of the zeolite template via electrostatic interactions. Pt metal clusters with a narrow size range of 0.89 to 1.22 nm have been obtained on the intersectional sites of beta-zeolite (Pt@beta) with a broad range of Si/Al molar ratios (15-200). The uniformly distributed Pt clusters in Pt@H-beta are subject to strong electron withdrawal by the zeolite, which promotes transfer of active hydrogen, providing excellent activity and stability in hydrodeoxygenation reactions. A general strategy is thus proposed for the encapsulation of subnanometric metal clusters in zeolites with high thermal stability.

4.
Plast Reconstr Surg ; 148(3): 543-547, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34432684

ABSTRACT

BACKGROUND: The improvement of nasolabial folds by either lateral superficial musculoaponeurotic system rhytidectomy or minimal access cranial suspension lift alone is commonly performed, but patient satisfaction is often limited in East Asians. An innovative technique, termed the cable-stayed face lift, which combines the strengths of lateral superficial musculoaponeurotic system rhytidectomy and minimal access cranial suspension lift, was developed for improved results. METHODS: Between 2016 and 2019, 20 cable-stayed face lifts were performed in a single hospital. Two plastic surgeons independently evaluated postsurgery outcomes using a five-point Likert scale, where 5 = excellent, 4 = good, 3 = fair, 2 = no change, and 1 = worse. Patient satisfaction was assessed by relevant items from the FACE-Q questionnaire. RESULTS: Twenty patients with a mean age of 51 years underwent face-lift surgery. The mean follow-up ± SD was 11.3 ± 9.8 months. The five-point Likert scale score evaluated by surgeons was 3.65 ± 1.08. Patient-perceived age visual analogue scale (7.8 ± 4.4) exhibited a difference between preoperative actual age and postoperative apparent age. Patients demonstrated high satisfaction with outcome (67.5 ± 16.2) and satisfaction with lower face and jawline (76.2 ± 14.9). No major complication, hematoma, or seroma was observed. CONCLUSION: The authors' approach-cable-stayed face lift-offers a good alternative to provide a more effective effacement of nasolabial folds, by lifting the nasolabial folds with parallel vector and lower face and neck with the vertical vector. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Nasolabial Fold/surgery , Rhytidoplasty/methods , Superficial Musculoaponeurotic System/surgery , Asian People , Esthetics , Female , Humans , Middle Aged , Nasolabial Fold/anatomy & histology , Patient Satisfaction , Rejuvenation , Treatment Outcome
5.
Ann Plast Surg ; 86(3S Suppl 2): S194-S198, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33651014

ABSTRACT

INTRODUCTION: Different from Western culture, prominent zygoma and rectangular facial contour are deemed as unaesthetic and masculine in Asians. To achieve an ideal oval facial shape, reduction malarplasty is often performed. METHODS: Twenty-two eligible patients who underwent reduction malarplasty between November 2008 and December 2018 were reviewed. The reduction malarplasty involved repositioning of the osteotomized zygomatic arch and subperiosteal lift via a limited temporal incision. Photographs were collected both preoperatively and postoperatively. Complications and postoperative outcomes were evaluated. RESULTS: Twenty-two patients underwent reduction malarplasty with subperiosteal lift between November 2008 and December 2018. Their mean age was 35 ± 2.30 years. Prominent zygoma and facial contour were significantly improved after surgery. Patients demonstrated satisfaction with outcome (73.77 ± 6.83) and with facial appearance (75.00 ± 5.60). No cheek drooping and major complications were observed during the long-term follow-up. CONCLUSIONS: Prominent zygoma treated with reduction malarplasty with subperiosteal lift via limited temporal incision has a stable and long-lasting effect. This approach can be regarded as a true alternative for facial contour reshaping.


Subject(s)
Osteotomy , Plastic Surgery Procedures , Adult , Cheek/surgery , Face , Humans , Zygoma/surgery
6.
Nanomaterials (Basel) ; 10(11)2020 Nov 12.
Article in English | MEDLINE | ID: mdl-33198370

ABSTRACT

Herein, Pt/HZSM-5 zeolite catalysts with different crystallite sizes ranging from nanosheet (~2 nm) to bulk crystals (~1.5 µm) have been prepared for the hydrodeoxygenation of guaiacol, and their effects on the reaction pathway and product selectivity were explored. HZSM-5 zeolites prepared by seeding (Pt/Z-40: ~40 nm) or templating (Pt/NS-2: ~2 nm) fabricated intra-crystalline mesopores and thus enhanced the reaction rate by promoting the diffusion of various molecules, especially the bulky ones such as guaiacol and 2-methoxycyclohexanol, leading to a higher cyclohexane selectivity of up to 80 wt % (both for Pt/Z-40 and Pt/NS-2) compared to 70 wt % for bulky HZSM-5 (Pt/CZ: ~1.5 µm) at 250 °C and 120 min. Furthermore, decreased crystallite sizes more effectively promoted the dispersion of Pt particles than bulky HZSM-5 (Pt/Z-400: ~400 nm and Pt/CZ). The relatively low distance between Pt and acidic sites on the Pt/Z-40 catalyst enhanced the metal/support interaction and induced the reaction between the guaiacol molecules adsorbed on the acidic sites and the metal-activated hydrogen species, which was found more favorable for deoxygenation than for hydrogenation of oxygen-containing molecules. In addition, Pt/NS-2 catalyst with a highly exposed surface facilitated more diverse reaction pathways such as alkyl transfer and isomerization.

8.
J Craniofac Surg ; 31(2): 340-342, 2020.
Article in English | MEDLINE | ID: mdl-31764550

ABSTRACT

Autologous costal cartilage graft is optimal for augmentation rhinoplasty but with complications including markedly visible graft margins and dorsal contour irregularities. Therefore, the authors introduced the diced costal cartilage graft to smoothen the margins of bilateral spreader graft for nasal dorsum augmentation. A total of 6 patients were recruited for this augmentation rhinoplasty. The pre- and postoperative photographs were taken for improvement evaluation. During a mean follow-up of 15 months, none of the patients developed major complications that may require removal or revision of the costal cartilage grafts. Five patients (80%) were very satisfied with the aesthetic outcome. This simple algorithm facilitates the substantial augmentation and removes the visibility of dorsal graft in the costal cartilage rhinoplasty for the East Asian population.


Subject(s)
Costal Cartilage/surgery , Rhinoplasty , Adult , Asian People , Female , Humans , Margins of Excision , Nose/surgery , Postoperative Period , Retrospective Studies , Transplantation, Autologous
9.
J Craniofac Surg ; 31(2): 372-376, 2020.
Article in English | MEDLINE | ID: mdl-31764560

ABSTRACT

PURPOSE: Despite many advances in the knowledge of vascular malformations, extracranial arteriovenous malformations (AVMs) remain an enigma and are usually misdiagnosed and mismanaged due to their associated rare morbidity. This study aimed to describe the clinical course and emphasize the progressive nature of AVMs through a retrospective study of 446 patients. METHODS: Patients with cutaneous and soft-tissue AVMs presenting to our Vascular Anomalies Center between March 2011 and March 2017 were reviewed. Medical records were examined for disease course, age at first presentation at our institution, distributions and locations of lesions, clinical staging, progression, and previous treatments. Progression was defined as advancement to a higher Schobinger stage from a lower stage. RESULTS: A total of 446 patients (mean age, 25.6 ±â€Š14.0 years) were enrolled in this study, including 232 (52.0%) males (gender ratio, 1.08:1). Arteriovenous malformations lesions in 76.7% (342/446) of the patients were located in the head and neck. Children with Stage I AVMs had a 41.9% risk of progression before adolescence and an 80.0% risk of progression before adulthood. Nearly all patients (96.2%) showed progression in adulthood. Diffuse lesions were more likely to progress than localized lesions (P < 0.05) in childhood and adolescence. Lesions in the head and neck regions were less likely to progress than those in other regions in childhood (P = 0.005). A total of 216 (48.4%) patients had undergone previous treatments. Among these patients, bleomycin showed an unintentional positive effect in the treatment of AVMs. CONCLUSIONS: Extracranial AVMs have a continuously progressive nature. A full understanding regarding the progressive course of AVMs can lead patients and physicians to attach importance to early diagnosis and management. Meanwhile exploring innovative treatments should be focused in the future to prevent potential destructive progression.


Subject(s)
Arteriovenous Malformations/diagnosis , Adolescent , Adult , Arteriovenous Malformations/therapy , Bleomycin/therapeutic use , Child , Combined Modality Therapy , Disease Progression , Female , Head/blood supply , Humans , Male , Neck/blood supply , Retrospective Studies , Treatment Outcome , Young Adult
10.
J Plast Reconstr Aesthet Surg ; 72(12): 2027-2032, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31648959

ABSTRACT

BACKGROUND: Tissue expanders can lead to bone deformity as well as bone resorption. Not all changes in the cranial bone can be completely normalised after tissue expander extraction. This study aimed to investigate the potential factors for persistent forehead deformities after tissue expansion. PATIENTS AND METHODS: Cases of forehead tissue expansion performed from 2011 to 2015 were retrospectively reviewed. Demographic and clinical data were collected. Two plastic surgeons (Y.Q. and C.Q.) evaluated changes in the forehead by comparing preoperative and most recent postoperative photographs. The Fisher exact, chi-square and Student t tests, and univariate and multivariate logistic regression analyses were performed in this study. RESULTS: Sixty-seven patients underwent forehead expanded flap reconstructions and continuous follow-ups were done in the outpatient service. The mean duration of the follow-ups after expander removal was 33.86 months. Overall, 28 (41.8%) patients had forehead changes. Age, sex, indications for tissue expansion and follow-up time were not associated with forehead changes. There were significant differences in the total injection volume and expansion period between patients with forehead changes (41.8%) and those without (58.2%). No significant negative correlation was found between the duration of pressure bandage usage post-operatively and the occurrence of forehead changes. CONCLUSIONS: Our recommendations for performing tissue expansion in the skull area are as follows: (1) always choose expanders with the largest base dimension; (2) perform tissue expansion as quickly as possible and (3) do not cause overexpansion. In addition, there was no proven benefit of using pressure bandages when skeletal changes occurred.


Subject(s)
Forehead/surgery , Surgical Flaps , Tissue Expansion/adverse effects , Adolescent , Adult , Child , Child, Preschool , Facial Asymmetry/etiology , Facial Asymmetry/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies , Tissue Expansion Devices/adverse effects , Young Adult
11.
Mutagenesis ; 34(4): 299-306, 2019 12 19.
Article in English | MEDLINE | ID: mdl-31613971

ABSTRACT

Arteriovenous malformation (AVM) is defined as a fast-flow vascular anomaly that shunts blood from arteries directly to veins. This short circuit of blood flow contributes to progressive expansion of draining veins, resulting in ischaemia, tissue deformation and in some severe cases, congestive heart failure. Various medical interventions have been employed to treat AVM, however, management of which remains a huge challenge because of its high recurrence rate and lethal complications. Thus, understanding the underlying mechanisms of AVM development and progression will help direct discovery and a potential cure. Here, we summarize current findings in the field of extracranial AVMs with the aim to provide insight into their aetiology and molecular influences, in the hope to pave the way for future treatment.


Subject(s)
Arteriovenous Malformations/diagnosis , Arteriovenous Malformations/genetics , Animals , Arteriovenous Malformations/metabolism , Biomarkers , Diagnosis, Differential , Disease Management , Disease Susceptibility , Embryonic Development/genetics , Genetic Association Studies , Genetic Loci , Genetic Predisposition to Disease , Humans , Mutation , Phenotype , Signal Transduction , Syndrome , Translational Research, Biomedical
12.
J Dermatol ; 46(11): 962-966, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31515846

ABSTRACT

Infantile hemangioma (IH) is a type of benign tumor that develops during infancy and spontaneously involutes after 1 year of age. Before the introduction of propranolol in 2008, some patients with IH were instructed to wait for the involution without treatment. This long-term follow-up study was conducted to assess the prognosis of East-Asian children with untreated deep or mixed facial IH. Skin sequelae were assessed by comparing images obtained during the patients' first and last visits in our clinic. Possible factors were assessed for their association with IH prognosis. The mean follow-up time was 7.4 years. Among the 48 patients with deep or mixed facial IH, 26 (54%) achieved complete involution without sequelae and 22 encountered various sequelae, including telangiectasia (36.3%), fibrofatty residue (68.2%), and scars (4%). The complete regression rate of deep or mixed IH occurring in the central facial region was significantly lower than for those in the perifacial region (33.3% vs 66.7%, respectively, χ2 , P = 0.025). Further, the most common sequelae in this area are fibrofatty residue.


Subject(s)
Hemangioma/therapy , Skin Neoplasms/therapy , Watchful Waiting , Asian People , Cardiovascular Agents/therapeutic use , Child , Child, Preschool , Conservative Treatment , Disease Progression , Face , Female , Follow-Up Studies , Hemangioma/complications , Humans , Male , Prognosis , Propranolol/therapeutic use , Remission, Spontaneous , Retrospective Studies , Skin/blood supply , Skin/pathology , Skin Neoplasms/complications
13.
Ann Plast Surg ; 83(4S Suppl 1): S70-S73, 2019 10.
Article in English | MEDLINE | ID: mdl-31513070

ABSTRACT

BACKGROUND: Prominent tear trough deformity and midfacial depression are the first priority in periorbital rejuvenation. To achieve harmonious lower eyelid improvement, we developed a novel approach to reposition infraorbital fat using intraoral anchoring in transconjunctival lower eyelid blepharoplasty. METHODS: Fourteen patients were included. Blepharoplasty involved infraorbital fat repositioning by intraoral anchoring via a transconjunctival incision to address depression and grooves deformities. Optimal fat repositioning can be achieved by intraorally manipulating suture tension. Photographs were taken both preoperatively and postoperatively. Time of operation, complications, recovery time, and postoperative outcomes were evaluated. RESULTS: Fourteen patients underwent blepharoplasty between August of 2018 and December of 2018. Their mean age was 36.9 ± 6.1 years. Grooves deformities and depression were eliminated, and the periorbital contour significantly improved. All patients were satisfied with postoperative outcomes. There were no major complications observed. CONCLUSIONS: Intraoral anchoring of the infraorbital fat pedicles yields a significantly improved lower eyelid appearance and requires minimum clinic visits and an extremely short recovery time. In addition, the maneuverable intraoral anchoring allows for customization of patient aesthetics. This approach can be regarded as a true alternative for lower lid rejuvenation, and the outcome is straightforward and predictable.


Subject(s)
Adipose Tissue/surgery , Blepharoplasty/methods , Adult , Female , Humans , Male , Middle Aged , Rejuvenation , Suture Techniques
14.
Ann Plast Surg ; 83(4S Suppl 1): S77-S81, 2019 10.
Article in English | MEDLINE | ID: mdl-31513072

ABSTRACT

BACKGROUND: Surgical management of cheek congenital melanocytic nevus (CMN) remains a huge challenge because of undesirable defects in repair. The use of direct closure is often limited to defect reconstruction with a diameter less than 4 cm. OBJECTIVE: This study aimed to evaluate the safety and efficacy of direct vertical closure combined with extensive subcutaneous tissue undermining boundaries for intermediate-to-large cheek defects. METHODS AND MATERIALS: A retrospective review was conducted to evaluate patients with cheek CMN who underwent the aforementioned procedure. Projected adult size, defect size, and incision length were measured. The Vancouver scar scale and visual analog scale were applied to assess scar formation and postoperative appearance. Complications within 1 year postoperatively were recorded. RESULTS: A total of 35 patients with CMN >3.5 cm underwent the procedure. Patients' age ranged from 3 to 36 years. The average projected adult size of the facial CMN was 5.5 ± 1.6 cm. The mean Vancouver scar scale and visual analog scale scores were 2.6 ± 1.0 and 8.0 ± 0.7, respectively. There were 2 cases of dog ear deformity (5.7%) and 1 case of hematoma (2.9%). CONCLUSION: This simple algorithm yields satisfying results with low complication rate in the repair of intermediate-to-large cheek defects and may become a useful alternative to cheek reconstruction.


Subject(s)
Cheek/surgery , Nevus, Pigmented/congenital , Nevus, Pigmented/surgery , Plastic Surgery Procedures , Skin Neoplasms/congenital , Skin Neoplasms/surgery , Adolescent , Adult , Algorithms , Child , Child, Preschool , Esthetics , Female , Humans , Male , Retrospective Studies
15.
J Vasc Surg Venous Lymphat Disord ; 6(5): 626-635, 2018 09.
Article in English | MEDLINE | ID: mdl-29752186

ABSTRACT

OBJECTIVE: The objective of this study was to assess the midterm and long-term results of patients with auricular arteriovenous malformations (AVMs) treated by ethanol embolization. METHODS: Medical records of 35 patients (20 male, 15 female; age range, 10-59 years) with auricular AVMs between 2006 and 2016 were reviewed. The short-term results of 4 of the 35 patients were reported in 2009. They were included in this study with updated follow-up data. The data from the 31 new included patients have not been reported previously. Ethanol embolization was performed with a direct puncture approach. The nidus was eradicated by bolus injection of ethanol with manual compression whenever possible. Treatment outcomes were classified into four categories by assessing the resolution of symptoms as well as the degree of nidus devascularization between the baseline and follow-up angiography studies. RESULTS: A total of 86 embolization sessions were performed in 35 patients (mean, 2.5 ± 1.3 sessions). The dosage of ethanol used per single session was 12.0 ± 4.5 mL (range, 6.0-24 mL). All patients received post-treatment clinical follow-up (mean, 40.7 ± 25.8 months), and 28 patients received post-treatment imaging follow-up (mean, 34.3 ± 25.5 months). Ethanol embolotherapy was effective in all patients. Control was achieved in 16 patients (45.7%), and improvement was achieved in 18 patients (51.4%). One patient experienced recurrence. A total of 13 minor complications and 2 major complications occurred in 12 patients during the 86 treatment sessions (12/35 [34.2%]; 15/86 [17.4%]). All the complications resolved spontaneously. CONCLUSIONS: The midterm and long-term results of this study demonstrate that ethanol embolization alone is an effective option for auricular AVMs as first-line therapy with a mild risk of minor and major complications.


Subject(s)
Arteriovenous Malformations/therapy , Ear, External/blood supply , Embolization, Therapeutic/methods , Ethanol/therapeutic use , Adolescent , Adult , Angiography , Arteriovenous Malformations/diagnostic imaging , Child , Ear, External/diagnostic imaging , Embolization, Therapeutic/adverse effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Treatment Outcome , Young Adult
16.
Pediatrics ; 141(Suppl 5): S425-S429, 2018 04.
Article in English | MEDLINE | ID: mdl-29610165

ABSTRACT

Kaposiform hemangioendothelioma (KHE) is a rare infiltrative vascular tumor that is potentially life-threatening when presenting with Kasabach-Merritt phenomenon (KMP). KMP is clinically characterized as severe thrombocytopenia and hypofibrinogenemia and therefore is associated with a high mortality rate. There is no standard of cure for KHE currently. Potential medications, including corticosteroids, propranolol, and chemotherapy drugs such as sirolimus, are often used for alleviating KHE symptoms. Although some case reports of sirolimus treatment have shown promising results with recovered coagulant parameters, the off-target effects may cause severe problems. Here we describe 2 cases of infant patients with KHE and KMP who were scheduled to receive sirolimus on a long-term basis. However, both patients developed paroxysmal cough and tachypnea shortly after the onset of sirolimus treatment and succumbed to infection thereafter. This report reveals a potential risk of infection in sirolimus-treated infant patients. The fatal complication highlights the importance of antibiotic prophylaxis and serum sirolimus level monitoring to ensure the safe use of sirolimus in the treatment of infant patients with KHE.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Bronchopneumonia/diagnosis , Hemangioendothelioma/drug therapy , Immunosuppressive Agents/adverse effects , Kasabach-Merritt Syndrome/drug therapy , Sarcoma, Kaposi/drug therapy , Sirolimus/adverse effects , Bronchopneumonia/microbiology , Fatal Outcome , Female , Humans , Infant , Infant, Newborn , Male , Mycoplasma pulmonis , Pneumonia, Mycoplasma/diagnosis , Sirolimus/therapeutic use
17.
Sci Rep ; 8(1): 2360, 2018 02 05.
Article in English | MEDLINE | ID: mdl-29403061

ABSTRACT

Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about biomechanical forces in the induction of MIF in endothelial cells (ECs). Here, we show that laminar shear stress (LS) inhibits the expression of MIF in ECs. By profiling the whole transcriptome of human coronary artery ECs under different shear stress, we found that athero-protective LS attenuates the expression of MIF whereas pro-atherosclerotic oscillatory shear stress (OS) significantly increased the expression of MIF. En face staining of rabbit aorta revealed high MIF immunoreactivity in lesser curvature as well as arterial bifurcation areas where OS is predominant. Mechanistically, we found that Krüpple like factor 2 (KLF2) is required for inhibition of MIF expression in ECs in the context of shear stress. Knockdown of KLF2 abolishes LS-dependent MIF inhibition while overexpression of KLF2 significantly attenuated MIF expression. Overall, the present work showed that MIF is a shear stress-sensitive cytokine and is transcriptionally regulated by KLF2, suggesting that LS exerts its athero-protective effect in part by directly inhibiting pro-inflammatory MIF expression.


Subject(s)
Endothelial Cells/metabolism , Gene Expression , Intramolecular Oxidoreductases/metabolism , Kruppel-Like Transcription Factors/metabolism , Macrophage Migration-Inhibitory Factors/metabolism , Stress, Mechanical , Stress, Physiological , Cells, Cultured , Gene Expression Profiling , Gene Expression Regulation , Humans , Intramolecular Oxidoreductases/genetics , Macrophage Migration-Inhibitory Factors/genetics
18.
Radiology ; 287(1): 194-204, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29237147

ABSTRACT

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Arteriovenous Malformations/drug therapy , Bleomycin/therapeutic use , Injections, Intralesional , Adolescent , Adult , Antibiotics, Antineoplastic/administration & dosage , Bleomycin/administration & dosage , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Pilot Projects , Prospective Studies , Treatment Outcome , Young Adult
19.
Sci Signal ; 10(464)2017 01 31.
Article in English | MEDLINE | ID: mdl-28143903

ABSTRACT

Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis. We investigated the function of TFEB in vascular biology and pathophysiology and demonstrated that TFEB in endothelial cells inhibited inflammation and reduced atherosclerosis development. Laminar shear stress, which protects against atherosclerosis, increased TFEB abundance in cultured primary human endothelial cells. Furthermore, TFEB overexpression in these cells was anti-inflammatory, whereas TFEB knockdown aggravated inflammation. The anti-inflammatory effect of TFEB was, at least, partially due to reduced oxidative stress because TFEB overexpression in endothelial cells decreased the concentrations of reactive oxygen species and increased the expression of the antioxidant genes HO1 (which encodes heme oxygenase 1) and SOD2 (which encodes superoxide dismutase 2). In addition, transgenic mice with endothelial cell-specific expression of TFEB exhibited reduced leukocyte recruitment to endothelial cells and decreased atherosclerosis development. Our study suggests that TFEB is a protective transcription factor against endothelial cell inflammation and a potential target for treating atherosclerosis and associated cardiovascular diseases.


Subject(s)
Atherosclerosis/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Endothelial Cells/metabolism , Inflammation/metabolism , Animals , Atherosclerosis/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Blotting, Western , Cells, Cultured , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Humans , Inflammation/genetics , Mice, Inbred C57BL , Mice, Transgenic , Oxidative Stress , RNA Interference , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism
20.
Physiol Genomics ; 48(9): 660-6, 2016 09 01.
Article in English | MEDLINE | ID: mdl-27449656

ABSTRACT

Atherosclerosis is a multifactorial disease that preferentially develops in specific regions in the arterial tree. This characteristic is mainly attributed to the unique pattern of hemodynamic shear stress in vivo. High laminar shear stress (LS) found in straight lumen exerts athero-protective effects. Low or oscillatory shear stress (OS) present in regions of lesser curvature and arterial bifurcations predisposes arterial intima to atherosclerosis. Shear stress-regulated endothelial function plays an important role in the process of atherosclerosis. Most in vitro research studies focusing on the molecular mechanisms of endothelial function are performed in endothelial cells (ECs) under cultured static (ST) condition. Some findings, however, are not recapitulated in subsequent translational studies, mostly likely due to the missing biomechanical milieu. Here, we profiled the whole transcriptome of primary human coronary arterial endothelial cells (HCAECs) under different shear stress conditions with RNA sequencing. Among 16,313 well-expressed genes, we detected 8,177 that were differentially expressed in OS vs. LS conditions and 9,369 in ST vs. LS conditions. Notably, only 1,618 were differentially expressed in OS vs. ST conditions. Hierarchical clustering of ECs demonstrated a strong similarity between ECs under OS and ST conditions at the transcriptome level. Subsequent pairwise heat mapping and principal component analysis gave further weight to the similarity. At the individual gene level, expressional analysis of representative well-known genes as well as novel genes showed a comparable amount at mRNA and protein levels in ECs under ST and OS conditions. In conclusion, the present work compared the whole transcriptome of HCAECs under different shear stress conditions at the transcriptome level as well as at the individual gene level. We found that cultured ECs are significantly different from those under LS conditions. Thus using cells under ST conditions is unlikely to elucidate endothelial physiology. Given the revealed high similarities of the endothelial transcriptome under OS and ST conditions, it may be helpful to understand the underlying mechanisms of OS-induced endothelial dysfunction from static cultured endothelial studies.


Subject(s)
Coronary Vessels/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Transcriptome/physiology , Atherosclerosis/metabolism , Cells, Cultured , Gene Expression Profiling/methods , Humans , RNA, Messenger/metabolism , Stress, Mechanical
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